Clopidogrel (S-(+)-(2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl) acetic acid methyl ester has the following structure (1)

It is available in the market as its bisulfate salt and is marketed by Sanofi-Synthelabo as “Plavix”.
Clopidogrel is an inhibitor of platelet aggregation and is marketed as an antianginal agent, antiplatelet agent and is found to decrease morbid events in people with established atherosclerotic cardiovascular disease and cerebrovascular diseases.
The therapeutic application of Clopidogrel as blood-platelet aggregation inhibiting agents and antithrombotic agent and its preparation is disclosed in U.S. Pat. Nos. 4,529,596. 4,847,265 describes the process for the preparation of the hydrogen sulfate salt of Clopidogrel wherein first the racemic base is obtained which is then resolved using (−) Camphor sulfonic acid [(−) CSA] to obtain the chirally pure base which is then converted to the corresponding salts such as sulfate, hydrochloride etc. salts.
Various other strategies to prepare Clopidogrel are disclosed in WO 98/51681, WO 98/51682, WO 98/51689, WO 99/18110, U.S. Pat. Nos. 5,036,156, 5,132,435, 5,139,170, 5,204,469 and 6,080,875 etc. all of which are incorporated herein as reference.
We have earlier disclosed improved processes for the manufacture of (S)-(+)-Clopidogrel base, its intermediates and its bisulfate salt [Indian Patent Applications 84/MUM/2001 (WO 02059128/U.S. Pat. No. 6,635,763), & 335/MUM/2001] which are cited herein in their entirety as reference. The process described therein may be represented as:

EP 1480985 (Helm AG) describes a process for purifying impure Clopidogrel base by treating the impure base with benzenesulfonic acid and subsequently hydrolyzing the salt to obtain the pure base.
In all prior art process, the Clopidogrel base needs to be resolved/chirally enriched using (−)-Camphor sulfonic acid salt. Such a process is expensive and hence industrially less suitable. The present inventors have surprisingly found that chemically and chirally pure Clopidogrel base can be prepared without the need for further treatment with camphor sulfonic acid, which is costly and less viable. The base so prepared could be used for preparing different salts.
We herein describe a novel process for preparing optically pure Clopidogrel base which does not require subsequent purification step, and is easy to scale up and operationally simple.